1,024 research outputs found

    Erchen Decoction Prevents High-Fat Diet Induced Metabolic Disorders in C57BL/6 Mice

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    Erchen decoction (ECD) is a traditional Chinese medicine prescription, which is used in the treatment of obesity, hyperlipidemia, fatty liver, diabetes, hypertension, and other diseases caused by retention of phlegm dampness. In this study we investigated the potential mechanism of ECD, using metabolism-disabled mice induced by high-fat diet. Body weight and abdominal circumference were detected. OGTT was measured by means of collecting blood samples from the tail vein. Blood lipid levels and insulin were measured using biochemical assay kit. Real-time PCR was used to measure the CDKAL1 gene expression and western blot was used to measure the protein expression. Through the research, it was found that ECD showed markedly lower body weight and abdominal circumference than those in the HFD group. Consistently, we observed that ECD significantly improved glucose tolerance, promoted the secretion of insulin and decreased the level of TG, TC level. Meanwhile, we observed significantly increased CDKAL1 mRNA and protein level in the ECD group. Therefore, we speculate that the potential molecular mechanism of ECD is to promote the CDKAL1 expression, ameliorate islet cell function, and raise insulin levels to regulate the metabolic disorder

    Establishment and assessments of a new model for the postoperative fatigue syndrome by major small intestinal resection in rats

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    Objective. Postoperative fatigue syndrome (POFS) is a general and main complication after surgery. However, there is no stable and standardized animal model for POFS. The aim of the present study was to establish a rodent model of POFS by small intestinal resection, with POFS evaluated by acknowledged physical and behavioral methods. Material and Methods. Forty-two Sprague-Dawley rats were randomly divided into four groups according to the length of a "middle" small intestinal resection: 0% (sham group; i.e., laparotomy alone), 10%, 40% and 70% groups, with corresponding lengths of small intestinal resections. Following surgery, the general state of health was evaluated. Tail suspension test, open field test and Morris water maze test were used to evaluate the degree of POFS. Serum albumin, transferrin, prealbumin and fibronectin were measured to assess the nutritional status, and superoxide dismutase (SOD) and malondialdehyde (MDA) were also measured. Results. As compared with the other three groups, the 70% small intestinal resection group showed the worst general state of health, decreased strength of the tail suspension test and decreased score of Morris water maze test (p < 0.05) after operation. All rats in whom the small intestinal resection was done demonstrated a certain degree of malnutrition and behavior of depression, and the 70% resection group had the lowest levels of transferrin, prealbumin and fibronectin as compared with the other groups (p < 0.05), as well as decreased SOD and increased MDA in serum (p < 0.05). Conclusions. Resection of 70% of the small intestine resulted in typical characteristics of POFS. As this procedure is simple, stable and easily reproducible, it may serve as a model for research on POFS

    Identification and characterization of a novel fumarase gene by metagenome expression cloning from marine microorganisms

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    <p>Abstract</p> <p>Background</p> <p>Fumarase catalyzes the reversible hydration of fumarate to <smcaps>L</smcaps>-malate and is a key enzyme in the tricarboxylic acid (TCA) cycle and in amino acid metabolism. Fumarase is also used for the industrial production of <smcaps>L</smcaps>-malate from the substrate fumarate. Thermostable and high-activity fumarases from organisms that inhabit extreme environments may have great potential in industry, biotechnology, and basic research. The marine environment is highly complex and considered one of the main reservoirs of microbial diversity on the planet. However, most of the microorganisms are inaccessible in nature and are not easily cultivated in the laboratory. Metagenomic approaches provide a powerful tool to isolate and identify enzymes with novel biocatalytic activities for various biotechnological applications.</p> <p>Results</p> <p>A plasmid metagenomic library was constructed from uncultivated marine microorganisms within marine water samples. Through sequence-based screening of the DNA library, a gene encoding a novel fumarase (named FumF) was isolated. Amino acid sequence analysis revealed that the FumF protein shared the greatest homology with Class II fumarate hydratases from <it>Bacteroides </it>sp. 2_1_33B and <it>Parabacteroides distasonis </it>ATCC 8503 (26% identical and 43% similar). The putative fumarase gene was subcloned into pETBlue-2 vector and expressed in <it>E. coli </it>BL21(DE3)pLysS. The recombinant protein was purified to homogeneity. Functional characterization by high performance liquid chromatography confirmed that the recombinant FumF protein catalyzed the hydration of fumarate to form <smcaps>L</smcaps>-malate. The maximum activity for FumF protein occurred at pH 8.5 and 55°C in 5 mM Mg<sup>2+</sup>. The enzyme showed higher affinity and catalytic efficiency under optimal reaction conditions: <it>K</it><sub>m</sub>= 0.48 mM, <it>V</it><sub>max </sub>= 827 μM/min/mg, and <it>k</it><sub>cat</sub>/<it>K</it><sub>m </sub>= 1900 mM/s.</p> <p>Conclusions</p> <p>We isolated a novel fumarase gene, <it>fumF</it>, from a sequence-based screen of a plasmid metagenomic library from uncultivated marine microorganisms. The properties of FumF protein may be ideal for the industrial production of <smcaps>L</smcaps>-malate under higher temperature conditions. The identification of FumF underscores the potential of marine metagenome screening for novel biomolecules.</p

    Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

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    Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment

    An Updated Search of Steady TeV γ\gamma-Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array

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    Using the data taken from Tibet II High Density (HD) Array (1997 February-1999 September) and Tibet-III array (1999 November-2005 November), our previous northern sky survey for TeV γ\gamma-ray point sources has now been updated by a factor of 2.8 improved statistics. From 0.00.0^{\circ} to 60.060.0^{\circ} in declination (Dec) range, no new TeV γ\gamma-ray point sources with sufficiently high significance were identified while the well-known Crab Nebula and Mrk421 remain to be the brightest TeV γ\gamma-ray sources within the field of view of the Tibet air shower array. Based on the currently available data and at the 90% confidence level (C.L.), the flux upper limits for different power law index assumption are re-derived, which are approximately improved by 1.7 times as compared with our previous reported limits.Comment: This paper has been accepted by hepn

    GTPase regulator associated with the focal adhesion kinase (GRAF) transcript was down-regulated in patients with myeloid malignancies

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    <p>Abstract</p> <p>Background</p> <p>GTPase regulator associated with the focal adhesion kinase (<it>GRAF</it>), a putative tumor suppressor gene, is found inactivated in hematopoietic malignancies by either genetic or epigenetic abnormalities. However, the expression level of <it>GRAF </it>gene has not yet been studied in leukemia. The aim of this study was to investigate the expression level of <it>GRAF </it>gene in those patients with myeloid malignancies including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and chronic myeloid leukemia (CML).</p> <p>Methods</p> <p>The expression levels of <it>GRAF </it>transcript were determined in 94 patients using real-time quantitative PCR (RQ-PCR). Clinical and laboratory data of these patients were collected and analyzed.</p> <p>Results</p> <p>The significantly decreased level of <it>GRAF </it>transcript was observed in three myeloid malignancies compared to controls. Within AML, there was no difference in the level of <it>GRAF </it>transcript among different FAB subtypes (<it>P </it>> 0.05). Difference was not observed in the amount of <it>GRAF </it>mRNA between CML at chronic phase and controls. As CML progressed, <it>GRAF </it>transcript significantly decreased. In MDS, three cases with 5q deletion had lower <it>GRAF </it>transcript than four without 5q deletion (median 0.76 vs 2.99) (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>our results demonstrate that the <it>GRAF </it>transcript is decreased in myeloid malignancies.</p
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